Dibenzoazabicycloalkanes



United States Patent 3,310,565 DIBENZOAZABICYCLOALKANES Eugene Galantay, Morristown, N.J., assignor to Sandoz Inc., Hanover, NJ. N0 Drawing. Filed June 3, H66, Ser. No. 555,933 a 24 Claims. (Cl. 260-288) This application is a continuation-in-part of my copending application Ser. No. 406,188, filed Oct. 23, 1964.

This invention provides two series of compounds (CH CH B e.g. dimethylaminoethyl; or -aminopropyl (CH CH -CH B) e.g. morpholinopropyl;

B is either primary amino (NH mono(lower)alkylamino, e.g. methylamino, isopropylamino. and butylamino; di(lower)alkylamino, e.g. dimethylamino, N- ethyl-N-isopropylamino and dipropylamino; lower alkyleneimino, e.g. ethyleneimino, pyrrolidyl and piperidyl; morpholino; thiomorpholino; piperazino; N-(N- loweralkyl)-piperazino, e.g. N-ethylpiperazino; N-(N'- 1oweralkanol)-piperazino, e.g. N-(y-hydroxypropyl) piperazino;

each of Y Y Y Y Y and Y is either a hydrogen 1 atom (H); lower alkoxy, e.g. methoxy, ethoxy, propoxy, isopropoxy and butoxy; a halogen atom, e.g. chlorine (Cl), fluorine (--F), iodine (I) and bromine (Br); or trifluoromethyl (CF with the proviso that a plurality of trifluoromethyl groups are not ortho to each other; and

Z is either an oxygen atom (=0), or a sulfur atom which differ from each other only with respect to the saturation of one carbon-to-carbon bond.' In series (a) the 'bond is a double bond, whereas a single "bond is correspondingly located in series (b). Each series of compounds also includes two classes. I In one class of each X is dimethylene (--CH CH in the other, trimethylethylene (CH CH -'CH Throughout the entire text each of R R B, Y Y Y Y Y Y Z and X has its .above ascribed meaning, as does (a) and (b), in the absence of an indication to the contrary.

e The compounds of this invention are all derived from the corresponding compound which is a key intermediate. This key intermediate is prepared from corresponding compounds III according to the following reactions:

yr 7 e X Y a Y Y The starting materials III'for the preparation of unsubstituted key intermediates IIa are 10,11-dihydro-5H- dibenzo[a,d]cyclohepten-S-one (where X is dimethylene) and 5,10,11,12-tetrahydrodibenzo[a,d]cycloocten 5 one (where X is trimethylene). Both of these starting materials are known. Corresponding starting materials with substituents Y Y Y Y Y and Y are prepared from available compounds according to standard procedures Well-known to the art-skilled. The substituents are unetfected by the reactions leading from the starting material III to the key intermediate 11a and by the reactions leading from "the key intermediate Ila to the final compounds I.

ReactionA is a condensation with t-butyl acetate and diethylaminomagnesium bromide to give the hydroxy ester IV. Reaction B is the Reformatsky reaction with R (|3 H-C O -O-(lower alkyl) followed by saponification and dehydration. Exemplifications of reactions A and B are known [Winthrop, Stanley 0., Davis, M. A., Myers, G. 8.; Gavin, J. G., Thomas, R., and Barber, R., New Psychotropic Agents,

Derivatives of Dibenzo[a,d]-1,4cycloheptadiene, J. Org.

j ene-sulfonic acid as catalyst. Reactions D and E (cyclization) are efieted either with a mixture of polyphosphoric acid and acetic acid or with trifluoroacetic anhydride, as exemplified. When other cyclization reagents are employed, side products are formed to a greater extent and/ or the desired product undergoes further reactions, e.g. dimerization and condensation.

From the key intermediate Ila compounds I are prepared according to the following reactions:

Alternatively, compounds IIb are prepared by either the hydrogenation or chemical reduction of compound V to the corresponding saturated acid, followed by ring closure.

Reactions F are directed to the saturation of a nonaromatic double bond. This is preferably accomplished by catalytic hydrogenation, e.g. with a platinum or palladium catalyst.

Reactions G are preferably the Schmidt Reaction, i.e. compound II is reacted with hydrazoic acid (or a salt thereof) in the presence of strong mineral acid, e.g. sulfuric acid. An alternative reaction is the Beckmann rearrangement of the oximes of compound II.

Reactions H are with phosphorus pentasulfide (P 8 e.g. by refluxing in pyridine.

Reactions I are alkylations of compound VI to prepare the corresponding compound VIII wherein R is other than a hydrogen atom (-H). The starting compound VI is first reacted with a strong base, e.g. sodium hydride (NaH) and sodium amide; the product is then reacted with wherein R is not a hydrogen atom; and W is either a chlorine atom (C1), a bromine atom (Br), an iodine atom (-I), mesyloxy or tosyloxy.

Compounds Ia are exemplified in Table I by the variables R R Y Y Y Y Y Y", X and Z. It is understood that these same variables also define the corresponding compounds Ib, which are also within the scope of this invitation. The tabulated compounds are merely exemplary and are not to be construed as limitative in any way. In the table in addition to standard symbols for elements there are also found the following:

Me for methyl,

Et for ethyl,

Pr for propyl,

iPr for isopropyl, and Bu for butyl.

Compounds VI are intermediates in the preparation of compounds VII and VIII; compounds VIII are intermediates in the preparation of compounds IX; compounds Ia and Ila are intermediates in the preparation of compounds Ib. Compounds I are pharmaceutically active compounds which have central nervous system (CNS) activity. They and their pharmaceutically acceptable "salts are useful as anti-hypertensives and anti-inflamma tories. In addition, some compounds are antihistamines (e.g., title compounds of Examples 16 and 18), sedatives and/ or tranquilizers (e.g., title compounds of Examples 16 and 17) and anticonvulsants (e.g., title compounds of Example 17).

Compounds I are administered either orally or parenterally in average daily doses of from 40 milligrams to 60 milligrams.

Each of the pharmaceutically active compounds of this invention may be, e.g. incorporated, for oral administration, in a tablet as the sole active ingredient. A typical tablet is constituted by from 1 to 2 percent binder, e.g. tragacanth; from 3 to 10 percent disintegrating agent, e.g. corn starch; from 2 to 10 pencent lubricant, e.g. talcum; from 0.25 to 1.0 percent lubricant, e.g. magnesium stearate; an average dosage of active ingredient; and q.s. percent of filler, e.g. lactose; all percentages being by weight. The tablets are prepared according to standardtabletting techniques, which are well-known in the art, employing the necessary amounts of conventional granu lating liquids, e.g. alcohol SD-30 and purified water. An

exemplary tabletting formulation for the instant active compounds is Parts Title compound of Example 7 Tragacanth 2 Lactose 64.5 Corn starch 5 Talcum V 3 Magnesium stearate 0.5

Alcohol SD-30, purified Water, qis.

Reference to pharmaceutically acceptable salts is limited to those compounds I wherein R is either fi-aminoethyl or y-aminopropyl. Only these amino groups form salts, either acid addition salts, e.g. hydrochloride, citrate, 5

tartrate and methanesulfonate, or quaternary ammonium salts, e.g. methiodide.

. 6 7 EXAMPLE 1 CHr-CHz 10 To a stirred solution of parts commercial polyphos- -phoric acid in 400 parts by volume of glacial acetic acid,

add in small portions 40 parts of 5-hydroxy-5-(carbo-tert.-

butoxymethyl)-10,1l-dihydro 5H dibenzo[a,d]cycloheptene 1 and maintain the resulting red solution at 100 1 J. Org. Chem., 27, 230 (1962).

for 15 hours. Pour the reaction mixture onto ice, and

TABLE I.EXEMPLARY COMPONENTS Ia- The following examples are merely illustrative. Those examples wherein X is ethylene, i.e. dimethylene, are

dissolve the resulting orange precipitate in chloroform. Wash the obtained chloroform solution with 2 N sodium q y illustrative of the C0fI$P011ding Ieactions and hydroxide solution to separate S-carboxymethylidene-l0,

products where X is trimethylene, and vice versa. Likewise, reactions wherein the benzene nuclei are either unsubstituted or are specifically substituted are illustrative of cor-responding reactions, wherein said nuclei are any of those within the scope contemplated by this invention.

In all of the example, the parts and percentages are by weight unless otherwise specified, and the temperatures are in degrees centigrade. The relationship between parts by weight and parts by volume is the same as that between the kilogram and the liter.

ll-dihydro-SH-dibenzo[a,d]cycloheptene; then evaporate the remaining chloroform solution to give 17.5 parts of the crude 6,7-dihydro-2H-benzo[j]benz[c,d]azulen-Z-one. Purify by chromatography on silica gel to separate the compound of this example from 5-methylidene-10,1l-dihydro-5H-dibenz0[a,d]cycloheptene [1.8 parts, melting point (M.P.) 56 to 58]. The pure product is an orange solid, M.P. 66 to 67; oxime, M.P. 134; dinitrophenylhydrazone, M.P. 258.

9 EXAMPLE 8 1,2,6,7-tetrahydr-(1 1 bH) -benzo [j] benz [c,d] azulen-2-one Shake a solution of 17.5 parts of 1'-rnethyl-6,7-dihydro- 2H benzo[j] benz[-c,d]azulen-Z-one in 250 parts of 1,2- dimethoxyethane with 2.0 parts of palladium-charcoal (5%) catalyst in a hydrogen atmosphere of 3000 p.s.i.-g. until hydrogen consumption ceases. Filter the resultant mixture and extract the catalyst with boiling chloroform. Evaporate the filtrate and extracts. Isolate l-methyl- 1,-2,6,7-tetrahydro (lllbH) benzo[j]benz[c,d]aZulen-2- one from the residue by crystallization.

EXAMPLE 2-chloro -5-( I '-carb0xy-1 '-ethylidene) -10,11-

dihydro-SH-dibenzo [a,d] cycloheptene React 50 parts of 2-chloro-10,1l-dihydro-SH-dibenzo [a,d]cyclohepten-5-one with 55 parts of ethyl OL-bI'OIIlO- propionate under the conditions generally known as the Reformatsky Reaction. Saponify the crude product by refluxing it with alcoholic potassium hydroxide and acidity to obtain crude 2-chloro-5-(1'-carboxy-1' ethy1idene)-10, 1l-dihydro-SH-dibenzo[a,d]cycloheptene, which is used without further purification in the following example.

EXAMPLE 11 CHiCH:

Reflux for 16 hours a mixture of 40 parts of crude 2- chloro 5 (1-carboxy-1-ethylidene)-10,1l-dihydro-SH- dibenzo[a,d]cycloheptene, 20 parts of red phosphorus, and 160 parts of 57% hydriodic acid. Cool, pour the reaction mixture onto ice, filter and wash the insoluble product. Reflux the resultant product with concentrated 10 ammonium hydroxide. Filter the ammonium hydroxide solution and acidity with dilute hydrochloric acid to pH 1. 2 chloro 5-(1'-carboxy-1-ethyl)-10,1l-dihydro-SH- dibenzo[a,d] cycloheptene separates as a solid.

EXAMPLE 12 1-methyl-9-chl0r0-1,2,6,7-tetrahydr0- (IIbH) benzo [1'] benz [03d] azulen-Z-one o HrCHQ Heat a mixture of 10 parts of 2-chloro-5-(1'-carboxyl ethyl) 10,1l-dihydro-5H-dibenzo[a,d]cycloheptene and 100 parts of polyphosphoric acid at 95 for minutes.. Pour the reaction mixture onto ice and filter to separate the crude 1-methyl-9-chloro-1,2,6,7-tetrahydro- (llbH) benzo[j]benz[c,d] azulen 2-one. Wash the crude product with dilute aqueous sodium hydroxide and water and purify by recrystallization.

EXAMPLE 13 2,3,7,8-tetrahydrodibenzo [f] ',k] cyclohepta [c] pyridin-Z-one CHrOH2 To a stirred mixture of 2.0 parts of sodium azide, 18 parts of glacial acetic acid and 15 parts of sulfuric acid, add dropwise over a ten-minute period at 55.to 65 a solution of 2.66 parts of crude 6,7-dihydro-2H-benzo[j] benz[c,d]azulen-2-one in glacial acetic acid. Maintain the reaction mixture at 55 for 30 minutes and then pour onto ice. Filter the resultant solid; then wash said solid with Water and dimethylformamide, and recrystallize same from 18 parts by volume of boiling dimethylformamide to obtain 1.90 parts of 2,3,7,8-tetrahydrod benzo[f] [j,k]cyclohepta[c]-pyridin-2-one, M.P. 279.

EXAMPLE 14 2,3,8,9-tetrahydro- [7H] -dibenz0[f] [k,l] cycloocta[c] pyridin-Z-one CHz-OHz-GHz To .a stirred mixture of 2.0 parts of sodium azide, 18 parts of glacial acetic acid, and 15 parts of sulfuric acid, add dropwise over a ten-minute period at 55 to 65 a solution of 2.70 parts of 2,6,7,8-tetrahydrocyclopenta[d,e] dibenzo[a,d]cycloocten 2 one in glacial acetic acid. Maintain the reaction mixture at 55 for 30 minutes and then pour onto ice. Filter the resultant solid; then wash said solid with water and diethylether. Recrystallize from ethanol to obtain 230 parts of 2,3,8,9-tetrahydro- 7H-dibenzo[f][k,1]cycloocta[c]pyridin-2-one, M.P. 290 to 293.

1 1 EXAMPLE 1s 1-methyl-2,3,7,8-tetrahydr0-dibenz0 [f] ',k]

cyclohepta [c] pyridin-Z-one C Hz H2 To a stirred mixture of 2.0 parts of sodium azide, 18 parts of glacial acetic acid, and 15 parts of sulfuric acid, add dropwise over a ten-minute period at 55 to 65 a solution of 2.70 parts of 1-methyl-6,7-dihydro-2H-benzo [j]benz[c,d]azulen-2-one in glacial acetic acid. Main tain the reaction mixture at 55 for 30 minutes, and then pour onto ice. Filter the resultant solid (title compound); then Wash said solid with Water.

EXAMPLE 16 3-methyl-2,3,7,8-Zetrahydr0dibenz0 [f] ',k] cyclohepfa[c] pyridin-Z-one CHz-CHz HC NOHS Admix with stirring 50 parts of 2,3,7,8-tetrahydrodibenzo[f] [j,k]cyclohepta[c]pyridin-2-one and 23 parts of freshly sublimed potassium tert.-butoxide in 500 parts of dimethyl sulfoxide. Continue stirring until the formation of the potassium salt of 2,3,7,8-tetrahydrodibenzo[f] [j,k]cyclohepta[c]pyridin-Z-one is complete. Strip oif the thereby-formed tert.-butyl alcohol in vacuo; then add 200 parts of methyl iodide. Filter 16 hours. Strip off the excess methyl iodide in vacuo; add Water to complete the separation of the product and filter to obtain 3-methyl- 2,3,7,8 tetrahydro-dibenzo[f] [j,k]cyclohepta[c]pyridin- 2-one, M.P. 198.

EXAMPLE 17 3-diethylaminoethyl-2,3,7,8-tetrahydro dibenzoLf] ',k] cyclohepta [c] pyridin-Z-one (3 02 H C N- 0 H2-- 0 Hz-N CsHs Reflux a mixture of 10 parts of 7,8-dihydro-2H-dibenzo [f][j,k]cyclohepta[c]pyridin-2-one, 1.92 parts of 53.3% sodium hydride mineral oil dispersion and 70 parts by volume of dry toluene until hydrogen evolution ceases.

' Cool mixture to 0 to 5 and add dropwise the solution 12 EXAMPLE l8 3-methyl-2,3,7,8-tetrahydrodibenzo [f] [j,k] c yclahepfa [c] pyridine-Z-thione CHrCHi l] 8 Heat a mixture of 9.3 parts of 3-methyl-2,3,7,8-tetrahydrodibenzo[f] [j,k]cyclohepta[c]pyridin-2-one and 10.0 parts of phosphorus pentasulfide in parts of pyridine under reflux for minutes. Cool, add gradually thereto 100 parts of Water, whereupon 3.5 parts of crude product crystallizes. Recrystallize from 700 parts of ethanol to obtain pure title compound, M.P. 169 to 170, dec.

EXAMPLE 19 2 ,3,7,8,9,l3b-hexahydr0 [1H] -dibenzo [f] [k,l]cycl0- 0cta[c]pyridin-2-0ne CHz-CHz-Ol-Iz Add two parts of sodium azide to an ice cold, stirred mixture of 5 parts of 1,2,6,7,8,12b-hexahydro-cyclopenta [d,e]dibenzo[a,d]cycloocten-2-one, 100 parts of chloroform and 80 parts of concentrated sulfuric acid. After nitrogen evolution ceases, pour mixture on ice and Work up chloroform layer to obtain the title compound.

EXAMPLE 2o 3-dimethy laminoethyl-2,3,7,8-tetrahydr0-dibenz0 [J] [j,k] cyclohep ta [0] pyridin-2-0ne Reflux a mixture of 15 parts of 7,8-dihydro-2H-dibenzo [f] [j,k]cyclohepta[c]pyridin-Z-one, 3.2 parts of a 53.3% sodium hydride mineral oil dispersion and-70 parts of volume of dry toluene until hydrogen evolution ceases. Cool mixture to 0 to 5 and add dropwise the solution of 22.6 parts of dimethylaminoethyl chloride in 70 parts by volume of dry toluene. After stirring at room temperature for 18 hours, reflux for 2 hours. Cool again, Wash mixture several times with water, dry and evaporate toluene layer. Treat residual oil, dissolved in dry diethylether, with an ethereal solution of hydrogen chloride to obtain the hydrochloride salt of the title compound, M.P. 196 to 200, dec.

It is thought that the invention and its advantages will be understood from the foregoing description. It is apparent that various changes may be made in the processes, the intermediates and the final products Without departing from the spirit and scope of the invention or sacrificing its material advantages. The products hereinbefore dein the scope of compounds I.

wherein R is a member selected from the group consisting of a hydrogen atom and lower alkyl; and each of Y Y Y Y Y and Y is a member selected from the group consisting of a hydrogen atom, lower alkoxy, a halogen atom and trifluoromethyl, no two trifluoromethyl groups being ortho to each other. 2. The compound of claim 1, which is 2,3,7,8-tetra hydrodibenzo [f] [j ,k] cyclohepta [c] pyridin-Z-one.

3. The compound of claim 1 which is 1-methyl-2,3,7,8- tetrahydrodibenzo [f [j,k] cyclohepta c] pyridin-2-one.

4. A compound of the formula wherein R is a member selected from the group consisting of a hydrogen atom and lower alkyl;

R is a member selected from the group consisting of lower alkyl, ar(1ower)alkyl, CH CH -B and B is a member selected from the group consisting of primary amino, mono(1ower) alkylamino, di(lower) alkylamino, lower alkyleneimino, morpholino, thiomorpholino, piperazino, N-(N-lower alkyl)-piperazinc and N-(N-lower alkanol)-piperazin;and

each of Y Y Y Y Y and Y is a member selected from the group consisting of a hydrogen atom, lower alkoxy, a halogen atom and trifluoromethyl, no two trifluoromethyl groups being ortho to each other.

5. The compound of claim 4 which is 3-methyl-2,3,7,8- tetrahydrodibenzo f] [j,k] cyclohepta [c] pyridin-Z-one.

6. The compound of claim 4 which is 3-dimethylaminoethyl 2,3,7,8 tetrahydrodibenzo[f] [j,k]cyclohepta[c] pyridin-Z-one.

7. The compound of claim 4 which is 3-dimethylaminoethyl 2,3,7,8 tet rahydrodibenzo[f][j,k]cyclohepta[c] pyridin-Z-one.

8. A compound of the formula wherein R is a member selected from the group consisting of a hydrogen atom and lower alkyl;

' each of Y Y Y Y Y and Y is a member selected from the group consisting of a hydrogen atom, lower alkoxy, a halogen atom and trifluoromethyl, no two trifluoromethyl groups being ortho to each other.

9. A "compound of the formula wherein R is a member selected from the group consisting of a hydrogen atom and lower alkyl; R is a member selected from the group consisting of lower alkyl, ar(lower)-alkyl, -CH CH B and B is a member selected from the group consisting of primary amino, mono(lower)alkylamino, di(lower) alkylamino, lower alkyleneimino, morpholino, thiomorpholino, piperazino, N-(N-lower a1kyl)-piperazino and N-(N'-lower alkanol)-piperazino; and

each of Y Y Y Y Y and Y is a member selected from the group consisting of a hydrogen atom; lower alkoxy, a halogen atom and trifluoromethyl, no two trifiuoromethyl groups being ortho to each other.

10. The compound of claim 9 which is 3-methyl-2,3,7,

8 tetrahydrodibenzo[f] [j,k] cyclohepta[c]pyridine 2 thione.

11. A compound of the formula wherein R is a member selected from the group consisting of a hydrogen atom and lower alkyl; and each of Y Y Y Y Y and Y is a member selected from the group consisting of a hydrogen atom, lower alkoxy, a halogen atom and trifluoromethyl, no two trifluoromethyl groups being ortho to each other. 12. The compound of claim 11 which is 2,3,8,9-tetrahydro- [7H] dibenzo [f] [k,l] cycloocta[c] pyridin-Z-one.

13. A compound of the formula wherein R is a member selected from the group consisting of a hydrogen atom and lower alkyl;

R is a member selected from the group consisting of lower alkyl, ar(lower)alkyl, -CH CH --B and B is a member selected from the group consisting of primary amino, mono(lower)alkylamino, di(lower)- alkylamino, lower alkyleneimino, morpholino, thiomorpholino, piperazino, N-(N-lower alkyl)-piperazino and N-(N'-lower alkanol)piperazino; and

each of Y Y Y Y Y and Y is a member selected from the group consisting of a hydrogen atom,

lower alkoxy, a halogen atom and trifluoromethyl, no two trifluoromethyl groups being ortho to each other. 14. A compound of the formula CHz-OHz-OHz NH R wherein R is a member selected from the group consisting of a hydrogen atom and lower alkyl; and each of Y Y Y Y Y and Y is a member selected from the group consisting of a hydrogen atom, lower alkoxy, a halogen atom and trifiuoromethyl, no two trifluoromethyl groups being ortho to each other. 15. A compound of the formula wherein R is a member selected fromthe group consisting of a hydrogen atom and lower alkyl; R is a member selected from the group consisting of lower alkyl, ar(lower) alkyl, CH -CH B and B is a member selected from the group consisting of primary amino, mono(lower)alkylamino, di(lower)alkylamino, lower alkyleneimino, morpholino, thiomorpholino, piperazino, N-(N'-lower alkyl)-piperazino and N-(N-lower alkanoD-piperazino; and

each of Y Y Y Y Y and Y is a member selected from the group consisting of a hydrogen atom, lower alkoxy, a halogen atom and trifluoromethyl, no two trifluoromethyl groups being ortho to each other. 16. A compound of the formula wherein R is a member selected from the group consisting of a hydrogen atom and lower alkyl; and

each of Y Y Y Y, Y and Y is a member selected from the group consisting of a hydrogen atom, lower alkoxy, a halogen atom and trifluoromethyl, no two trifluoromethyl groups being ortho to each other.

17. The compound of claim 16 which is 2,3,7,8,9,l3b-

hexahydro 1H]dibenzo [f] [k,l] cycloocta [c] pyridin-2-one.

18. A compound of the formula wherein R is a member selected from the group consisting of a hydrogen atom and lower alkyl;

R is a member selected from the group consisting of lower alkyl, ar(lower)alkyl, -CH -CH ,B and B is a member selected from the group consisting of primary amino, mono(lower)alkylamino, di(lower) alkylamino, lower alkyleneimino, morpholino, thiomorpholino, piperazino, N-(N'-lower alkyl)-piperazino and N-(N-lower alkanol)-piperazino; and

each of Y Y Y Y Y and Y is a member selected from the group consisting of a hydrogen atom, lower alkoxy, a halogen atom 'and trifluoromethyl, no two trifiuoromethyl groups being ortho to each other.

19. A compound of the formula I wherein R is a member selected from the group consisting of a hydrogen atom and lower alkyl; and

each of Y Y Y Y Y and Y is a member selected from the group consisting of a hydrogen atom, lower alkoxy, a halogen atom and trifluoromethyl, no two trifluoromethyl groups being ortho to each other.

20. A compound of the formula wherein R is a member selected from the group consisting of a hydrogen atom 'and lower alkyl;

R is a member selected from the group consisting of lower alkyl, ar(lower)alkyl, -CH CH B and CH CH CH -B;

B is a member selected from the group consisting of primary amino, mono(lower)all ylamino, di(lower) alkylamino, lower alkyleneimino, morpholino, thiomorpholino, piperazino, N-(N-lower alkyl)-piperazino and N-(N'-lower alkanoD-piperazino; and

each of Y Y Y Y Y and Y is a member selected from the group consisting of a hydrogen atom, lower alkoxy, a halogen atom and trifiuoromethyl, no two trifiuoromethyl groups being ortho to each other.

17 21. A compound of the formula wherein R is a member selected from the group consisting of a hydrogen atom and lower alkyl; and

each of Y Y Y Y Y and Y is a member selected from the group consisting of a hydrogen atom, lower alkoxy, a halogen atom and trifluoromethyl, no two trifluoromethyl groups being ortho to each other.

22. A compound of the formula wherein R is a member selected from the group consisting of a hydrogen atom and lower alkyl;

R is a member selected from the group consisting of lower alkyl, ar(lower)alkyl, --CH --CH ,B and B is a member selected from the group consisting of primary amino, mono(lower)alkylamino, di(lower) alkylamino, lower alkyleneimino, morpholino, thiomorpholino, piperazino, N-(N-lower alkyl)-piperazino "and N-(N-lower alkanol)-piperazino; and

each of Y Y Y Y Y and Y is a member selected from the group consisting of a hydrogen atom, lower alkoxy, a halogen atom and trifluoromethyl, no two 18 trifluoromethyl groups being ortho to each other. 23. A compound of the formula wherein R is a member selected from the group consisting of a hydrogen atom and lower alkyl; and

each of Y Y Y Y, Y and Y is a member selected from the group consisting of a hydrogen atom, lower alkoxy, 'a halogen atom and tnifluoromethyl, no two trifiuoromethyl groups being ortho to each other.

24. A compound of the formula No references cited.

ALEX MAZEL, Primary Examiner. DONALD G. DA'US, Assistant Examiner. 

4. A COMPOUND OF THE FORMULA
 6. THE COMPOUND OF CLAIM 4 WHICH IS 3-DIMETHYLAMINOETHYL-2,3,7,8-TETRAHYDRODIBENZO (F) (J,K)-CYCLOHEPTA (C) PYRIDIN-2-ONE. 